Intervention-specific association of weight variability with major adverse cardiovascular events in overweight or obese adults with type 2 diabetes mellitus
Abstract Background Weight variability is associated with cardiovascular outcomes in diabetic patients. However, the effect of higher weight variability caused by intensive lifestyle intervention (ILI) on cardiovascular outcomes in diabetic patients is not well established. We aimed to evaluate the intervention-specific association between weight variability with major adverse cardiovascular event (MACE) among overweight or obese adults with diabetes. Methods In 3,859 participants from the Action for Health in Diabetes (Look AHEAD) trial, multivariate-adjusted Cox regression models were used to evaluate the associations of weight variability measured by variability independent of the mean (VIM) with MACE and secondary outcomes in intensive lifestyle intervention (ILI) and diabetes support & education (DSE) arm, respectively. Results During a median follow-up of 9.6 years, 255 (12.9%) participants in the ILI arm and 247 (13.2%) participants in the DSE arm developed MACE. Participants with the highest quartile of weight variability (VIM Q4) experienced a 2.23-fold higher risk of MACE compared with the lowest quartile (VIM Q1) in the DSE arm (hazard ratio [HR] 2.23; 95% CI 1.51–3.30), but not the ILI arm (HR 1.05; 95% CI 0.73–1.50). Moreover, compared with the lowest weight variability (VIM Q1), participants with the highest weight variability (VIM Q4) were not associated with all secondary outcomes in the ILI arm (all P>0.05) but were associated with the higher risks of secondary cardiovascular composite outcome (HR 1.88; 95% CI 1.20–2.95), all-cause mortality (HR 3.19; 95% CI 1.75–5.82), and myocardial infarction (HR 1.95; 95% CI 1.12–3.37) in the DSE arm. Conclusions Among the overweight or obese individuals with type 2 diabetes mellitus, rising weight variability was independently associated with increased MACE risks in the DSE arm but not the ILI arm. Therefore, a guideline-recommended ILI strategy for weight loss should be adopted to improve cardiovascular outcomes without considering the effect of high weight variability. FUNDunding Acknowledgement Type of funding sources: None.